title: Telaprevir-based triple therapy for chronic hepatitis C patients with advanced fibrosis: a prospective clinical study.
abstract: BACKGROUND
  Antiviral treatment is recommended for chronic hepatitis C patients with advanced fibrosis to reduce and prevent cirrhosis-related complications.
  
  
  OBJECTIVE
  To evaluate the efficacy and safety of telaprevir (TVR)-based triple therapy for patients with advanced fibrosis in a clinical practice setting.
  
  
  METHODS
  This prospective, multicentre study consisted of 102 patients with advanced fibrosis (METAVIR score F3-4) who were infected with HCV genotype 1b. All received 12 weeks of TVR in combination with 24 weeks of pegylated interferon (PEG-IFN) α2b and ribavirin (RBV).
  
  
  RESULTS
  The sustained virological response (SVR) rate was 69.6% (71 of 102). Notably, for treatment-naïve and prior relapse patients the SVR rate was over 80%. Previous treatment response, interleukin 28B polymorphism (rs8099917) and rapid virological response (undetectable HCV RNA at week 4) were independently associated with SVR. To achieve SVR, an adequate dosage of PEG-IFNα2b (≥1.2 μg/kg/week) and RBV (≥7.5 mg/kg/day) is preferable; however, the mean weight-adjusted TVR dosage had little impact on treatment outcome. Although severe blood cytopaenia and a dermatological disorder were frequently found, the rate of discontinuation due to adverse effects was 12.7%. The inosine triphosphatase CC allele (rs1127354) was independently associated with the development of severe anaemia, and lower serum albumin level (<35 g/L) was associated with the occurrence of infection.
  
  
  CONCLUSIONS
  The great gain in the SVR rate by telaprevir-based triple therapy offsets the problems with adverse effects; thus, it should be considered as a potent treatment protocol for patients with advanced fibrosis, especially for those with treatment-naïve and prior relapse.
authors.affiliation: Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Ogawa
authors.forename: N
authors.initials: N
authors.lastname: Furusyo
authors.forename: M
authors.initials: M
authors.lastname: Nakamuta
authors.forename: E
authors.initials: E
authors.lastname: Kajiwara
authors.forename: H
authors.initials: H
authors.lastname: Nomura
authors.forename: K
authors.initials: K
authors.lastname: Dohmen
authors.forename: K
authors.initials: K
authors.lastname: Takahashi
authors.forename: T
authors.initials: T
authors.lastname: Satoh
authors.forename: K
authors.initials: K
authors.lastname: Azuma
authors.forename: A
authors.initials: A
authors.lastname: Kawano
authors.forename: Y
authors.initials: Y
authors.lastname: Tanabe
authors.forename: K
authors.initials: K
authors.lastname: Kotoh
authors.forename: S
authors.initials: S
authors.lastname: Shimoda
authors.forename: J
authors.initials: J
authors.lastname: Hayashi
mesh_terms: D000368:Aged; D000740:Anemia / Q000453:epidemiology / Q000209:etiology; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D012008:Recurrence; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D009842:Oligopeptides; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C486464:telaprevir; C417083:peginterferon alfa-2b